scholarly journals Imaging Biomarkers in Animal Models of Drug-Induced Lung Injury: A Systematic Review

2020 ◽  
Vol 10 (1) ◽  
pp. 107
Author(s):  
Irma Mahmutovic Persson ◽  
Karin von Wachenfeldt ◽  
John Waterton ◽  
Lars Olsson ◽  
Keyword(s):  
Animal Models ◽  
Lung Injury ◽  
Lung Disease ◽  
Data Extraction ◽  
Exposure Dose ◽  
Imaging Modalities ◽  
Imaging Biomarkers ◽  
Drug Induced ◽  
Imaging Results

For drug-induced interstitial lung disease (DIILD) translational imaging biomarkers are needed to improve detection and management of lung injury and drug-toxicity. Literature was reviewed on animal models in which in vivo imaging was used to detect and assess lung lesions that resembled pathological changes found in DIILD, such as inflammation and fibrosis. A systematic search was carried out using three databases with key words “Animal models”, “Imaging”, “Lung disease”, and “Drugs”. A total of 5749 articles were found, and, based on inclusion criteria, 284 papers were selected for final data extraction, resulting in 182 out of the 284 papers, based on eligibility. Twelve different animal species occurred and nine various imaging modalities were used, with two-thirds of the studies being longitudinal. The inducing agents and exposure (dose and duration) differed from non-physiological to clinically relevant doses. The majority of studies reported other biomarkers and/or histological confirmation of the imaging results. Summary of radiotracers and examples of imaging biomarkers were summarized, and the types of animal models and the most used imaging modalities and applications are discussed in this review. Pathologies resembling DIILD, such as inflammation and fibrosis, were described in many papers, but only a few explicitly addressed drug-induced toxicity experiments.

Systematic review: In vivo imaging in animal models relevant to drug-induced Interstitial lung disease (DIILD)

2018 ◽  
Author(s):  
Irma Mahmutovic Persson ◽  
Karin Von Wachenfeldt ◽  
Kashmira Pindoria ◽  
Juan A. Delgado-San Martin ◽  
Simon Campbell ◽  
...  
Keyword(s):  
Systematic Review ◽  
Interstitial Lung Disease ◽  
Animal Models ◽  
Lung Disease ◽  
In Vivo Imaging ◽  
Drug Induced

scholarly journals Longitudinal Imaging Using PET/CT with Collagen-I PET-Tracer and MRI for Assessment of Fibrotic and Inflammatory Lesions in a Rat Lung Injury Model

2020 ◽  
Vol 9 (11) ◽  
pp. 3706 ◽  
Author(s):  
Irma Mahmutovic Persson ◽  
Nina Fransén Pettersson ◽  
Jian Liu ◽  
Hanna Falk Håkansson ◽  
Anders Örbom ◽  
...  
Keyword(s):  
Lung Injury ◽  
Imaging Techniques ◽  
Collagen I ◽  
Imaging Biomarkers ◽  
Drug Induced ◽  
Non Invasive ◽  
Pet Tracer ◽  
Pet Ct ◽  
Activity Measurements ◽  
Longitudinal Imaging

Non-invasive imaging biomarkers (IBs) are warranted to enable improved diagnostics and follow-up monitoring of interstitial lung disease (ILD) including drug-induced ILD (DIILD). Of special interest are IB, which can characterize and differentiate acute inflammation from fibrosis. The aim of the present study was to evaluate a PET-tracer specific for Collagen-I, combined with multi-echo MRI, in a rat model of DIILD. Rats were challenged intratracheally with bleomycin, and subsequently followed by MRI and PET/CT for four weeks. PET imaging demonstrated a significantly increased uptake of the collagen tracer in the lungs of challenged rats compared to controls. This was confirmed by MRI characterization of the lesions as edema or fibrotic tissue. The uptake of tracer did not show complete spatial overlap with the lesions identified by MRI. Instead, the tracer signal appeared at the borderline between lesion and healthy tissue. Histological tissue staining, fibrosis scoring, lysyl oxidase activity measurements, and gene expression markers all confirmed establishing fibrosis over time. In conclusion, the novel PET tracer for Collagen-I combined with multi-echo MRI, were successfully able to monitor fibrotic changes in bleomycin-induced lung injury. The translational approach of using non-invasive imaging techniques show potential also from a clinical perspective.

scholarly journals Imaging pheochromocytoma in small animals: preclinical models to improve diagnosis and treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hermine Mohr ◽  
Alessia Foscarini ◽  
Katja Steiger ◽  
Simone Ballke ◽  
Christoph Rischpler ◽  
...  
Keyword(s):  
Animal Models ◽  
Ex Vivo ◽  
Therapy Response ◽  
Human Cell Line ◽  
Mouse Cell ◽  
Cardiovascular Complications ◽  
Imaging Modalities ◽  
Life Threatening ◽  
Early Tumor

AbstractPheochromocytomas (PCCs) and paragangliomas (PGLs), together referred to as PPGLs, are rare chromaffin cell-derived tumors. They require timely diagnosis as this is the only way to achieve a cure through surgery and because of the potentially serious cardiovascular complications and sometimes life-threatening comorbidities that can occur if left untreated. The biochemical diagnosis of PPGLs has improved over the last decades, and the knowledge of the underlying genetics has dramatically increased. In addition to conventional anatomical imaging by CT and MRI for PPGL detection, new functional imaging modalities have emerged as very useful for patient surveillance and stratification for therapy. The availability of validated and predictive animal models of cancer is essential for translating molecular, imaging and therapy response findings from the bench to the bedside. This is especially true for rare tumors, such as PPGLs, for which access to large cohorts of patients is limited. There are few animal models of PPGLs that have been instrumental in refining imaging modalities for early tumor detection, as well as in identifying and evaluating novel imaging tracers holding promise for the detection and/or treatment of human PPGLs. The in vivo PPGL models mainly include xenografts/allografts generated by engrafting rat or mouse cell lines, as no representative human cell line is available. In addition, there is a model of endogenous PCCs (i.e., MENX rats) that was characterized in our laboratory. In this review, we will summarize the contribution that various representative models of PPGL have given to the visualization of these tumors in vivo and we present an example of a tracer first evaluated in MENX rats, and then translated to the detection of these tumors in human patients. In addition, we will illustrate briefly the potential of ex vivo biological imaging of intact adrenal glands in MENX rats.

Pivotal role of the HMGB1/sRAGE axis in drug-induced lung injury in advanced lung cancer with pre-existing interstitial lung disease

2020 ◽  
Author(s):  
Satoshi Nakao ◽  
Yamaguchi Kakuhiro ◽  
Shinjiro Sakamoto ◽  
Yasushi Horimasu ◽  
Takeshi Masuda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Interstitial Lung Disease ◽  
Lung Injury ◽  
Lung Disease ◽  
Pivotal Role ◽  
Advanced Lung Cancer ◽  
Drug Induced

scholarly journals Imaging Biomarkers and Pathobiological Profiling in a Rat Model of Drug-Induced Interstitial Lung Disease Induced by Bleomycin

2020 ◽  
Vol 11 ◽  
Author(s):  
Irma Mahmutovic Persson ◽  
Hanna Falk Håkansson ◽  
Anders Örbom ◽  
Jian Liu ◽  
Karin von Wachenfeldt ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Rat Model ◽  
Imaging Biomarkers ◽  
Drug Induced

Association between Maturation and Aging and Pulmonary Responses in Animal Models of Lung Injury

2015 ◽  
Vol 123 (2) ◽  
pp. 389-408 ◽  
Author(s):  
Laura R. A. Schouten ◽  
Marcus J. Schultz ◽  
Anton H. van Kaam ◽  
Nicole P. Juffermans ◽  
Albert P. Bos ◽  
...  
Keyword(s):  
Animal Models ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Intracellular Signaling ◽  
Meta Analysis ◽  
Pulmonary Inflammation ◽  
Age Groups ◽  
Qualitative Comparison ◽  
In Vivo Models

Abstract Background: Advanced age is associated with an increased susceptibility and mortality of the acute respiratory distress syndrome. This may be due to the progressive changes in innate immune responses and intrinsic properties of the lung that occur during the process of aging. Therefore, this study assesses the association between maturation and aging and pulmonary responses to injury in animal models of lung injury. Methods: A systematic search was conducted in PubMed, EMBASE (up to June 2014) and in the references of relevant articles to identify the studies using in vivo models of lung injury caused by an acute pulmonary insult, in which at least two age groups were compared. Because methodological diversity precluded combining these studies in a quantitative meta-analysis, data are presented based on the qualitative comparison with the adult group. Results: Of the 2,840 identified studies, 51 were included in this review. Most studies showed that, in response to a pulmonary insult, increasing age is associated with more pulmonary inflammation, edema, alveolar damage, and higher mortality. In addition, results indicate the existence of age-dependent changes in key components of the intracellular signaling pathways involved in the inflammatory response. Conclusions: Increasing age seems to be correlated with exaggerated pulmonary responses to injury, ultimately leading to more severe lung injury. Pulmonary inflammation seems relatively suppressed in infants/juveniles, whereas in the middle aged/elderly, the inflammatory response seems delayed but aggravated. This implies that investigators and clinicians need to use caution about extrapolating results from adolescent or youngadult animals to pediatric or elderly patients in clinical practice.

scholarly journals In Vivo Tracking of Extracellular Vesicles by Nuclear Imaging: Advances in Radiolabeling Strategies

2020 ◽  
Vol 21 (24) ◽  
pp. 9443
Author(s):  
Sara Almeida ◽  
Liliana Santos ◽  
Amílcar Falcão ◽  
Célia Gomes ◽  
Antero Abrunhosa
Keyword(s):  
Extracellular Vesicles ◽  
Covalent Binding ◽  
Cell Communication ◽  
Nuclear Imaging ◽  
High Sensitivity ◽  
Imaging Modalities ◽  
Biological Behavior ◽  
Imaging Biomarkers ◽  
Special Focus

Extracellular vesicles (EVs) are naturally secreted vesicles that have attracted a large amount of interest in nanomedicine in recent years due to their innate biocompatibility, high stability, low immunogenicity, and important role in cell-to-cell communication during pathological processes. Their versatile nature holds great potential to improve the treatment of several diseases through their use as imaging biomarkers, therapeutic agents, and drug-delivery vehicles. However, the clinical translation of EV-based approaches requires a better understanding of their in vivo behavior. Several imaging technologies have been used for the non-invasive in vivo tracking of EVs, with a particular emphasis on nuclear imaging due to its high sensitivity, unlimited penetration depth and accurate quantification. In this article, we will review the biological function and inherent characteristics of EVs and provide an overview of molecular imaging modalities used for their in vivo monitoring, with a special focus on nuclear imaging. The advantages of radionuclide-based imaging modalities make them a promising tool to validate the use of EVs in the clinical setting, as they have the potential to characterize in vivo the pharmacokinetics and biological behavior of the vesicles. Furthermore, we will discuss the current methods available for radiolabeling EVs, such as covalent binding, encapsulation or intraluminal labeling and membrane radiolabeling, reporting the advantages and drawbacks of each radiolabeling approach.

scholarly journals Novel imaging approaches for small animal models of lung disease (2017 Grover Conference series)

2018 ◽  
Vol 8 (2) ◽  
pp. 204589401876224 ◽  
Author(s):  
Isaac P. Pinar ◽  
Heather D. Jones
Keyword(s):  
Animal Models ◽  
Lung Disease ◽  
Small Animal ◽  
Pulmonary Vasculature ◽  
Technological Advances ◽  
X Ray Imaging ◽  
Large Airways ◽  
Small Animal Models ◽  
Lung Health

Imaging in small animal models of lung disease is challenging, as existing technologies are limited either by resolution or by the terminal nature of the imaging approach. Here, we describe the current state of small animal lung imaging, the technological advances of laboratory-sourced phase contrast X-ray imaging, and the application of this novel technology and its attendant image analysis techniques to the in vivo imaging of the large airways and pulmonary vasculature in murine models of lung health and disease.

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